The Radiation Sciences Program brings together laboratory and clinical investigators and clinicians Interested in the biological effects of radiation and the use of radiation therapy for cancer treatment. The program consists of 26 members from 8 different departments. Since the last funding cycle the research base for the Radiation Sciences Program increased 48% from $4,142,697 to $6,112,068 total annual direct research support, of which $4,065,571 is from the NCI. Over this last grant period, there were 278 publications of Radiation Science Program members, of which 18.7% are intra-programmatic and 44.2% are inter-programmatic. The members are divided into two chief interest groups: The biology interest group consists of investigators studying basic mechanisms of how cells respond to DNIA-damaging agents. A better understanding of these fundamental basic mechanisms in normal and cancer cells is critical in guiding the development of improved use of radiation in the clinic. Some of the specific areas studied by members of this interest group Include: Induction of DNA damage; mechanisms of DNA double strand break repair; regulation of DNA damage signal transduction; activation of cell cycle checkpoints; mechanisms of DNA damage-induced cell death; gene therapy for cancer treatment; molecular targets of radiosensitization; DNA damage-induced gene expression; mechanism of replication stress in cancer cells; and, genomic instability. The medical physics Interest group consists of investigators applying physics to the practice of radiation oncology. This group has a long track record of developing novel highly conformal radiation therapy techniques. This group has strong interactions with many clinical programs in the Cancer Center including Head and Neck, GI, Lung, Breast, and Prostate. In addition, this group has worked with clinicians in neuro-oncology and with the Molecular Imaging Program to develop new methods of functional imaging in the CNS. Specific topics of Interest include developing new methods of: dose calculation; optimization; assessment and correction of geometric uncertainties; image registration; constructing 4-D models of patients for planning; treatment delivery; and, imaging patients or tumors in real time during treatment.